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启动子甲基化与乳腺癌患者中SMAD4表达降低相关。

Promoter methylation correlates with reduced SMAD4 expression in patients with breast cancer.

作者信息

Chaudhary Archana, Kumar Manish, Mohan Lalit, Haque Rizwanul, Prabhakar Pankaj, Ola Mohammad Shamsul, Ahmad Md Margoob

机构信息

Department of Pharmacology, Indira Gandhi Institute of Medical Sciences, Sheikhpura, Patna, 800014, Bihar, India.

Department of Surgical Oncology, Indira Gandhi Institute of Medical Sciences, Sheikhpura, Patna, 800014, Bihar, India.

出版信息

Discov Oncol. 2025 Aug 6;16(1):1484. doi: 10.1007/s12672-025-02966-6.

Abstract

PURPOSE

Over the past decades, there is a dramatic rise in the mortality and incidence rates of breast cancer globally, despite the progressive advancement of therapeutic options. Late detection of breast cancer is often the main culprit for the ineffective treatment, and death in patients. Finding breast cancer biomarkers is thus of significant importance. Epigenetic modifications are associated with up and down regulation of important biomarker in the TGF-β pathway, such as SMAD4, which may have a greater impact in the growth and poor prognosis in breast cancer. In the current investigation we are going to check how SMAD4 regulate in various Breast cancer patients? And how its epigenetic modifications play crucial role in disease prognosis?

METHODS

Twenty eight samples of patients with proven breast cancer and the adjacent normal tissue from the same patients were analyzed for SMAD4 expression using real-time PCR and Western blot. Additionally, MS-PCR was employed to detect the epigenetic and genetic alterations.

RESULT

SMAD4 expression dropped from Grade 1 to Grade 3 breast cancer both at mRNA and protein level as justified by real time PCR as well as western blot. This down regulation of SMAD4 expression is due to its promoter methylation, which may be a major contributing reason to the dysregulated production of SMAD4 in instances of breast cancer.

CONCLUSION

According to these findings, SMAD4 status assessment in breast cancer, fine-needle biopsy specimens may offer further prognostic data. Worse prognosis was linked to reduced SMAD4 expression due to promoter methylation in Breast cancer.

摘要

目的

在过去几十年里,尽管治疗方案不断进步,但全球乳腺癌的死亡率和发病率仍急剧上升。乳腺癌的晚期发现往往是治疗无效和患者死亡的主要原因。因此,寻找乳腺癌生物标志物至关重要。表观遗传修饰与TGF-β信号通路中重要生物标志物(如SMAD4)的上调和下调有关,这可能对乳腺癌的生长和不良预后产生更大影响。在本研究中,我们将研究SMAD4在不同乳腺癌患者中是如何调控的?以及其表观遗传修饰在疾病预后中如何发挥关键作用?

方法

使用实时PCR和蛋白质印迹法对28例经证实患有乳腺癌的患者样本及其同一患者的相邻正常组织进行SMAD4表达分析。此外,采用甲基化特异性PCR检测表观遗传和基因改变。

结果

实时PCR和蛋白质印迹法证实,从1级到3级乳腺癌,SMAD4在mRNA和蛋白质水平上的表达均下降。SMAD4表达的这种下调是由于其启动子甲基化,这可能是乳腺癌病例中SMAD4产生失调的主要原因。

结论

根据这些发现,在乳腺癌细针穿刺活检标本中评估SMAD4状态可能会提供更多预后数据。乳腺癌中由于启动子甲基化导致SMAD4表达降低与预后较差有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c41a/12328851/719d9edc4bc0/12672_2025_2966_Fig1_HTML.jpg

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